Metaproteomics based subtypes in muscle invasive bladder carcinoma and association with survival.

ObjectiveTo evaluate the effect of postoperative pathological findings related to the eligibility of adjuvant immunotherapy on oncologic outcomes in patients with localized and locally advanced muscle‐invasive bladder carcinoma (MIBC) and upper tract urothelial carcinoma (UTUC).Patients and methodsWe retrospectively evaluated 1082 patients treated with radical cystectomy (n = 597) and nephroureterectomy (n = 485) between January 2000 and April 2021. Patients were divided into two groups: pT3‐4 or pN+ without neoadjuvant chemotherapy and ypT2‐4 or pN+ treated with neoadjuvant chemotherapy (trial‐eligible group) or others (trial‐ineligible group). The primary outcome was the effect of trial eligibility for adjuvant immunotherapy on disease‐free survival (DFS) and overall survival (OS). Secondary outcomes included the additional effect of lymphovascular invasion (LVI) status to the clinical trial criteria on prognosis and a risk model development.ResultsThe median ages of the patients were 69 and 72 years in the MIBC and UTUC groups, respectively. Fifty‐two percent of patients met the trial inclusion criteria. Trial eligibility was significantly associated with poor DFS and OS among patients with MIBC and UTUC. LVI‐positive status was significantly associated with poor prognosis among patients in the trial‐eligible group. A very high risk (LVI+ or pN+ among the pT3‐4 or ypT2‐4) was significantly associated with poor prognosis.ConclusionA total of 52% of patients were eligible for adjuvant immunotherapy. Trial eligibility was significantly associated with a poor prognosis. LVI+ and pN+ may play a key role in candidate selection for adjuvant immunotherapy.

Impact of lymph node dissection in radical cystectomy for bladder cancer: How many vs how far?

With the significant clinical benefits of antibody-coupled drugs (ADCs) against HER2, the HER2-low-expressing population has come into focus. HER2-low-expressing patients express this membrane protein despite the absence of HER-2 amplification. Whether there is a difference in outcome and prognosis between patients with HER2-low expression and those with HER2-0 expression has not yet been clarified, and more clinical data are needed to characterize them. Clinical and pathological data of HER2-low versus HER2-0-expressing breast cancer patients treated with neoadjuvant chemotherapy (NACT) and operated at Xinjiang Uygur Autonomous Region Cancer Center from 2015 to 2018 were reviewed, and the patients were analyzed and studied in terms of pathologic complete response (PCR), overall survival (OS) and disease-free survival (DFS). A total of 283 breast cancer patients were included, 102 (36.04%) with HER2-0 expression and 181 (63.96%) with HER2-low expression, with clinical stage II-III. After the study, the pCR rates of HER2-0 and HER2-low tumors were found to be 19.61% and 11.05%, respectively, which were not statistically different (p=0.071); there were also no significant differences in the pCR rates in both hormone receptor-positive (HR+) and negative (HR-) subgroups of patients. DFS and OS were analyzed for all patients, and there was no statistically significant difference in DFS (p=0.16) and OS (p=0.33) between HER2-0 and HER2-low cases; however, in the HR- subgroup, DFS was worse in HER2-low patients (p=0.027), yet there was no statistically significant difference in OS (p=0.24); in the HR+ subgroup, the HER2 status was not associated with DFS and OS. We also analyzed DFS and OS in PCR and nonPCR patients, and there was no statistically significant difference in DFS (p=0.29) and OS (p=0.54) between HER2-0 and HER2-low cases in PCR patients, and no difference in DFS and OS between HER2-0 and HER2-low cases in nonPCR patients. In breast cancer patients receiving neoadjuvant chemotherapy, no significant differences in chemosensitivity or prognostic outcomes were observed between HER2-low and HER2-0 tumors, considering HR expression subtypes and other current clinicopathological features.

Introduction: The aim of this study was to evaluate the prognostic value of the number of lymph nodes removed in breast cancer patients who undergo axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC). Methods: We included patients who were diagnosed with invasive breast cancer and cytology with proven involved axillary node metastasis at diagnosis and treated with NAC followed by curative surgery at Samsung Medical Center between January 2007 and December 2015. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Results: Among 772 patients with NAC and ALND, there were 285 ypN0, 258 ypN1, 135 ypN2, and 94 ypN3 cases. The median follow-up duration was 69.0 months. The group with less than 10 lymph nodes number (<10 nodes group) included 123 patients and the group with 10 or more lymph nodes number (≥10 nodes group) included 649 patients. There were no significant differences in DFS (p = 0.501) or OS (p = 0.883) between the two groups. In the ypN0 subgroup, the <10 nodes group had worse DFS than ≥10 nodes group (p = 0.024). In the ypN1 subgroup, there were no significant differences in DFS (p = 0.846) or OS (p = 0.774) between the two groups. In the ypN2 subgroup, the <10 nodes group had worse DFS (p = 0.025) and OS (p = 0.031) than ≥10 nodes group Conclusion: In ypN0 and ypN2 subgroups, breast cancer patients with less than 10 lymph nodes number in ALND after NAC might be considered for additional staging or closer surveillance when compared to patients with 10 or more than lymph node.

PurposeIn the present study, we aimed to evaluate the initial tumor location as a prognostic factor in breast cancer patients treated with neoadjuvant chemotherapy (NAC).MethodsBetween March 2002 and January 2007, a total of 179 patients with stage II/III breast cancer underwent NAC followed by breast surgery. Using physical and radiologic findings, patients were grouped by their initial tumor location into inner/both quadrant (upper/lower inner quadrant involvement +/− multicentric tumor involving outer quadrant; n=97) and outer quadrant (n=82) tumor groups. All patients received neoadjuvant docetaxel/doxorubicin chemotherapy. One hundred two patients underwent modified radical mastectomy and 77 patients underwent breast-conserving surgery. Adjuvant radiotherapy (RT) and hormonal therapy were administered after surgery when indicated. While 156 patients underwent postoperative RT, 23 did not. The median follow-up duration was 61.1 (12–106) months.ResultsThe 5-year disease-free survival (DFS) and overall survival rates of all patients were 74.8% and 89.9%, respectively. Patients with inner/both quadrant tumors had lower 5-year DFS than those with outer quadrant tumors (67.7% vs. 83.4%, respectively; hazard ratio [HR]=1.941, p=0.034). A nodal ratio >25% was also an independent adverse prognostic factor for DFS (HR=3.276; p<0.001). There was no significant difference in DFS (p=0.592) after RT on the internal mammary node (IMN). Treatment failed in 44 out of 179 patients (24.6%), of which 27 patients had inner/both quadrant tumors. Twenty-one out of 27 patients had distant failures.ConclusionAmong breast cancer patients treated with NAC, those with inner/both quadrant tumors had lower DFS than those with outer quadrant tumors. More aggressive neoadjuvant and/or adjuvant chemotherapy with IMN RT is required for improved disease control and long-term survival.

Background Lobular breast cancer (ILC) has been reported to be associated with a lower rate of pathologic complete response (pCR) and breast conserving surgery following neoadjuvant chemotherapy compared with ductal carcinoma (IDC). ILC is predominantly oestrogen receptor positive, HER-2-ve and histologic grade 1 or 2. Oestrogen receptor positive breast cancer has been shown to have poorer responses to neoadjuvant chemotherapy. HER-2 positivity is associated with better responses to anthracycline based neoadjuvant chemotherapy than HER-2 negative, and substantially improved pathological complete response (pCR) rates relative to HER-2 negative disease with the use of HER-2 targeted agents in this patient group. This study investigates response and disease free survival of ILC compared with IDC. Methods Patients with ILC and IDC treated with neoadjuvant chemotherapy were identified from the prospectively collated breast unit database at the Royal Marsden Hospital. Demographic, tumour, treatment and outcome data was obtained from the database and hospital electronic patient record system. Statistical analysis was undertaken comparing IDC and ILC. Clinical response rates, pCR rates, breast conserving surgery rates, and disease free survival were analysed. Clinical response was defined as those with partial response (≥50% reduction in the product of breast tumour size from baseline measurement), or complete clinical response (no clinically palpable breast tumour). Subgroup analysis was performed on ER+ve, HER-2–ve and HER-2 unknown cases. Results A total of 1017 patients were identified. Of these, there were 920 IDC and 97 ILC cases. Median age at commencement of neoadjuvant chemotherapy was 47.9 years (range 23.6-74.9). Median follow-up was 7.6 years (range 0.2-26.5). Pathologic response rates were available for 717 patients. 119 (19%) IDC had pCR, and 1 (1.1%) ILC (p &amp;lt;0.001). Of the patients with clinical response data available, 762 (82.8%) of the IDC and 74 (76.3%) of the ILC had a clinical response (p 0.19). Of the 804 IDC patients who underwent surgery, 480 (59.7%) had breast conserving surgery, while of the 89 lobular patients 33 (37.1%) underwent breast conserving surgery (&amp;lt;0.0001). Median disease free survival was 10.9 years (95%CI 8.6-13.2) for IDC and 10.1 years (95%CI 7.3-12.9) for ILC (p 0.318). Within the ER+ve, HER2-ve/unknown group there were 403 IDC and 82 lobular patients. pCR results were available for 148 (30%) of the patients. 41 (15.8%) in the IDC and 1 (1.3%) in the ILC group had pCR (p=0.001). 335 (83.1%) in the IDC group and 64 (78.0%) in the ILC group had a clinical response (p 0.27). Breast conserving surgery rates were 212 (57.6%) in the ductal group and 30 (39.0%) in the lobular group (p 0.003). Conclusion Within the cohort entire rates of pCR and of breast conserving surgery were lower for those with ILC compared with IDC. Despite lower rates of pCR and breast conserving surgery in ILC, there was no difference in clinical response rates or in disease free survival compared with IDC. Significant differences in pCR and breast conserving surgery rates between ILC and IDC persisted on subgroup analysis of those with ER+ve HER2-ve/unknown breast cancer. Citation Format: Hilary L Martin, Geraldine Walsh, Komel Khabra, Tabitha Skinner, Ian E Smith. Neoadjuvant chemotherapy in invasive lobular breast carcinoma: Comparison of response, surgery and disease free survival with invasive ductal carcinoma [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-11-05.

P-152 Real-world data in patients with localized esophageal and gastro-esophageal junction cancer undergoing surgery in France: Results from the FREGAT database

The aim of this study was to compare the efficacy of adjuvant radiotherapy (RT) versus adjuvant chemoradiotherapy (CRT) in patients with salivary gland tumors (SGTs). Data from patients who underwent adjuvant RT for a diagnosis of SG cancer at Ankara Atatürk Education and Research Hospital, Ankara Numune Education and Research Hospital and Ankara Bilkent City Hospital between September 01, 2009 and September 01, 2022 were analysed retrospectively. We evaluated the efficacy of RT alone versus CRT in these patients in terms of acute response, treatment tolerance, overall survival (OS), and disease-free survival (DFS). Fifty-five patients who underwent RT between September 14, 2009 and August 04, 2022 at Ankara Atatürk Education and Research Hospital, Ankara Numune Education and Research Hospital and Ankara Bilkent City Hospital were included in this study. Eight patients who did not meet the study criteria were excluded; thus, the analysis was performed for 47 patients. The median follow-up period was 60 months (range: 6-160 months). The median patient age was 53 years (range: 18-86 years). Thirty-nine patients (83%) had parotid tumors and eight patients (17%) had submandibular cancer. The time from surgery to RT was 48 days (range: 20-126 days). Intensity-modulated radiotherapy was administered to all patients and the median RT dose was 66 Gy (range: 52-70 Gy). Concomitant chemotherapy (CCT) (40 mg/m 2 of cisplatin weekly) was administered to 13 patients (27.7%). Acute adverse events were observed in 17 patients (36.2%). Interruption of RT was noted for only six patients (12.8%), and this proportion did not differ significantly between the CRT and RT-only arms ( P = 0.538). Acute side effects were observed in 17 patients (36.2%), and there were no significant relationships between acute side effects and the administration of CCT ( P = 0.112). Recurrence was observed in 10 patients (21.3%). All recurrences were locoregional and no distant metastases were observed during the follow-up period. The median DFS of the patients was 48 months (range: 4-160 months), 1-year DFS was 86%, 2-year DFS was 83.5%, and 5-year DFS was 77.9%. There was no statistically significant difference in DFS between the adjuvant CRT and RT-alone arms ( P = 0.114). At the date of last follow-up, 14 patients (29.8%) had died. The median OS of the patients was 58.5 months (range: 6-160 months), 1-year OS was 91.4%, 2-year OS was 86.8%, and 5-year OS was 78%. There was no statistically significant difference in OS between the adjuvant CRT and RT-only arms ( P = 0.453). Stage was identified as the most important prognostic factor for DFS and OS. No significant differences in OS, DFS, or acute side effects were observed between the CRT and RT-only arms. Additional studies are needed to identify the subgroup of SGT patients for which CRT is most warranted.

Objectives This study explores variations in hormone receptor (HR) status between biopsy and post-operative reports, as well as changes following neoadjuvant chemotherapy (NACT). The correlation between HR status alterations and patient survival outcomes is the key focus of this investigation. Material and Methods This retrospective study conducted at a tertiary care center in Kolkata, Eastern India, from 2013 to 2018. Results The parameters of 482 breast cancer patients meeting inclusion criteria were studied. The majority were &gt;40 years (68.2%), with 300 receiving NACT. Clinical staging distribution was I (2.9%), IIA (10.4%), IIB (22.2%), IIIA (34.3%), IIIB (28.6%), and IIIC (1.6%). Preoperative and postoperative staging changes occurred in 47.7%, with 38.8% downstaging and 13.5% upstaging. Estrogen receptor (ER), progesterone receptor (PR), and Her2neu positivity at diagnosis were observed in 46.3%, 41.9%, and 36.9% of patients, respectively. Postoperative ER, PR, and Her2neu positivity were 46.1%, 40%, and 37.3%, respectively. Recurrence in 33.6% of patients correlated with factors like age, tumor grade, lymphovascular invasion (LVI), Perineural invasion (PNI), postoperative stage, ER, PR, and their changes. Multivariate analysis identified age, PNI, postoperative stage, stage change, ER, and PR changes as independent factors for recurrence. The correlation study demonstrated a significant association between NACT and changes in PR status (χ2 = 16.56; p = 0.001), while no significant associations were found for ER and Her2neu changes. Analysis of variance (ANOVA) revealed a substantial association between NACT and PR status changes (p = 0.001). Post Hoc tests indicated significant differences in PR status changes related to NACT. Kaplan-Meier survival analysis revealed a significant difference in disease-free survival (DFS) based on changes in ER and PR status, with ER-positive patients having a median DFS of 76 months and PR-positive patients showing a median DFS of 47 months. No significant DFS difference was observed for changes in Her2neu status. Conclusion Changes in hormone receptor status, particularly ER and PR, significantly impacted recurrence and DFS. The study highlights the importance of personalized management strategies, with age, tumor grade, lymphovascular invasion (LVI), and changes in ER and PR status identified as key factors influencing prognosis.

Background: Tumor regression grade (TRG) is a measure of histopathological response to neoadjuvant therapy (NAT). Post-therapy lymph node (ypN) metastasis was reported as a prognostic factor. However, the evaluation of the treatment effectiveness of NAT has not been well studied. Here, we explored whether TRG combined with ypN status could be a prognostic factor for gastroesophageal junction (GEJ) and gastric cancer (GC). Methods: 376 patients with GEJ or GC receiving NAT in Peking University Cancer Hospital were retrospectively collected from January 1, 2003 to June 30, 2021. According to TRG and ypN status, patients were innovatively categorized into four groups: TRG0N0, TRG1-3N0, TRG0-1N+, and TRG2-3N+. We applied Kaplan-Meier method and log-rank test to examine the differences in disease free survival (DFS) and overall survival (OS) among four groups. Univariate and multivariate analyses were performed to elucidate the relationships between TRG combined with ypN status and prognosis. Results: We observed significant survival differences among the four groups (P &amp;lt; 0.001, respectively). Median DFS and OS of patients with TRG0N0, TRG1-3N0 and TRG0-1N+ were not reached, whereas median DFS and OS of patients with TRG2-3N+ were 17.37 months (95%CI, 14.14 to 20.60 months) and 39.97 months (95%CI, 27.05 to 52.89 months). TRG combined with ypN status was an independent predictor for both DFS (P &amp;lt; 0.001) and OS (P &amp;lt; 0.001) in multivariate analysis. Additionally, TRG combined with ypN status was significantly associated with different NAT (P &amp;lt; 0.001). The TRG0N0 rate in patients accepting immunotherapy was 31.9%, which was the highest in all regimens. Conclusion: Our results demonstrate that TRG combined with ypN status is a novel independent predictor of both DFS and OS in resectable, locally advanced GEJ and GC. Neoadjuvant immunotherapy achieved the highest TRG0N0 rate. Citation Format: Hongyan Yin, Qian Yao, Keren Jia, Dongfeng Niu, Xiaoyi Chong, Yanyan Li, Xujiao Feng, Yilin Li, Lin Shen, Yang Chen. Tumor regression grade combined with post-therapy lymph node status: A novel independent prognostic factor for patients treated with neoadjuvant therapy followed by surgery in resectable, locally advanced gastroesophageal junction and gastric carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6748.

Optimal margin width for breast-conserving therapy (BCT) after neoadjuvant chemotherapy (NAC) is unknown. We sought to determine the impact of margin width on local recurrence and survival after NAC and BCT. Patients treated with NAC and BCT for stage I-III breast cancer from 2002 to 2014 were identified. Multivariate Cox regression was performed to determine the relationship between margin width and local recurrence free-survival (LRFS), disease-free survival (DFS), and overall survival (OS). A total of 382 patients were included. Median age was 51years [range 22-79], median tumor size 3.0cm [range 0.6-11.0], and receptor subtypes included 144 (37.7%) HR-/HER2-, 47 (12.3%) HR-/HER2+, 118 (30.9%) HR+/HER2-, and 70 (18.3%) HR+/HER2+. Breast pathologic complete response (pCR) was achieved in 105 (27.5%) patients. Final margin status was positive in 8 (2.1%) patients, ≤ 1mm in 65 (17.0%), 1.1-2mm in 30 (7.9%), and > 2mm in 174 (45.5%). The 5-year LRFS was 96.3% (95% CI 94.0-98.6), DFS was 85.5% (95% CI 81.8-90.7), and OS was 90.8% (95% CI 87.4-94.2). There was no difference in LRFS, DFS, or OS for margins ≤ 2 versus > 2mm, and no difference in DFS or OS for margins ≤ 1 versus > 1mm. HR+ subtype (p = 0.04) and pCR (p = 0.03) were correlated with favorable DFS and node negativity (p < 0.001) with favorable DFS and OS. In this cohort treated with NAC and BCT, there was no association between margin width and LRFS, DFS, or OS. Although further studies are needed, the excellent long-term outcomes demonstrated in patients with close (≤ 2mm) margins following NAC suggest that a margin of "no-ink-on-tumor" may be acceptable in appropriately selected patients.

Background:Epithelial-mesenchymal transition (EMT) plays an important role in bladder carcinoma (BC) invasiveness and metastasis. Studies have shown that muscle-invasive BC (MIBC) and non-MIBC (NMIBC) are different at the molecular level owing to different EMT-related programming. Recent studies suggest that dysregulation of specific miRNAs is linked to EMT in BC. With this background, we aimed to study the immunoexpression of EMT-markers and its correlation with miRNA-200c expression in a series of MIBCs and NMIBCs.Materials and Methods:Quantitative real-time-polymerase chain reaction for the quantification of miR-200c expression was performed on 50 cases of urinary BC obtained from transurethral resection of bladder tumor (TURBT), cystectomy specimens, and ten peritumoral bladder tissue. Immunohistochemistry for ZEB1, ZEB2, TWIST, E-cadherin, and β-catenin was performed on tumor and peritumoral bladder tissue.Results:Thirty-five TURBT and 15 cystectomy specimens were assessed. Among MIBC, loss of expression of E-cadherin (72.3%), β-catenin (66.7%), and ZEB1, ZEB2, and TWIST2 immunoreactivity was noted in 53.3%, 86.7%, and 73.3% of cases, respectively. Among NMIBC, loss of expression of E-cadherin (22.5%), β-catenin (17.1%) and ZEB1, ZEB2, and TWIST immunoreactivity was noted in 11.5%, 51.4%, and 91.4% of cases, respectively. Upregulation of miRNA-200c was noted in cases with retained E-cadherin and negative TWIST expression. Downregulation of miRNA-200c expression was noted in all the cases showing loss of E-cadherin, β-catenin, and in cases immunoreactive for ZEB1, ZEB2, and TWIST in MIBC. Downregulation of miRNA-200c expression was also noted in cases of MIBC with retained β-catenin and those immunonegative for ZEB1 and ZEB2. A similar trend was noted in NMIBC. Median miRNA-200c expression was low in both high-grade and low-grade NMIBC compared to peritumoral bladder tissue and was not statistically significant.Conclusion:This study for the first time explores the relation of miR200C with E-cadherin, b-catenin, and its direct transcriptional regulators, namely Zeb1, Zeb2, and Twist in the same cohort of BC. We observed that miRNA-200c is downregulated in both MIBC and NMIBC. We identified novel expression of TWIST in cases of BC showing downregulation of miR200Cs suggesting that it is one of the protein targets of altered miRNA-200c expression contributing to EMT and can serve as a promising diagnostic marker and therapeutic target. Loss of E-cadherin and ZEB1 immunoexpression in high-grade NMIBC suggests an aggressive clinical behavior. However, ZEB2 heterogeneous expression in BC limits its diagnostic and prognostic utility.

Introduction: The aim of this study was to compare the disease-free survival (DFS) and overall survival (OS) of patients who underwent interval cytoreductive surgery after 3–4 cycles or 6 cycles of neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer patients. Methods: Out of 219 patients with advanced epithelial ovarian cancer, 123 patients received 3–4 cycles and 96 patients received 6 cycles of platinum-based NACT. Afterward, laparotomy was performed for interval cytoreductive surgery. Results: No statistically significant difference was found for DFS and OS of the patients who received 3–4 cycles and those who received 6 cycles of NACT (HR: 1.047, 95.0% CI [0.779–1.407]; p: 0.746 for DFS, and HR: 1.181, 95.0% CI [0.818–1.707]; p: 0.368 for OS). Evaluating 123 patients who received 3–4 cycles of NACT, 87 patients (70.7%) without macroscopic residual tumor after interval cytoreductive surgery had significantly longer DFS and OS compared to 36 patients (29.3%) with any residual tumor (HR: 1.830, 95.0% CI [1.194–2.806]; p: 0.003 for DFS, and HR: 1.946, 95.0% CI [1.166–3.250]; p: 0.009 for OS). 96 patients who received 6 courses of NACT were evaluated; 63 patients (65.6%) without macroscopic residual tumor after interval cytoreductive surgery had significantly longer DFS and OS than 33 patients (34.4%) with any residual tumor (HR: 1.716, 9 5.0% CI [1.092–2.697]; p: 0.010 for DFS, and HR: 1.921, 95.0% CI [1.125–3.282]; p: 0.013 for OS). Conclusion: In patients with advanced ovarian cancer, there is no significant difference in DFS and OS between 3 and 4 cycles or 6 cycles of NACT. The most important factor determining survival is whether macroscopic residual tumor tissue remains after interval cytoreductive surgery following NACT.

BackgroundLymphopenia has been associated with inferior cancer outcomes, but there is limited data in breast cancer. We describe the effects of neoadjuvant chemotherapy on circulating immune cells and its association with pathological complete response (pCR) rates in triple negative breast cancer (TNBC).MethodsWe constructed a database of patients with early stage TNBC treated with neoadjuvant chemotherapy. Circulating lymphocytes and monocytes were assessed before and after neoadjuvant chemotherapy. These were correlated with pCR rates and disease‐free survival (DFS) using Fisher's exact test, logistic regression, and the log‐rank test.ResultsFrom 2000 to 2015, we identified 95 eligible patients. Median age was 50; 29 (31%) were treated with platinum‐containing chemotherapy; and 66 (69%) with nonplatinum‐containing chemotherapy (anthracycline‐taxane, or either alone). About 32 (34%) patients achieved a pCR; and 33 (35%) had recurrence events. Median follow‐up time was 47 months. No significant associations were found between changes in lymphocytes and pCR or DFS. There was a correlation between lower monocyte levels after neoadjuvant chemotherapy and pCR (mean monocyte 0.56 in those with no‐pCR vs 0.46 in those with pCR, P = .049, multivariate P = .078) and DFS (median DFS in highest monocyte quartile was 30 vs 107 months in lowest quartile, P = .022, multivariate P = .023). In patients who received nonplatinum regimens, DFS was better among those who had larger decreases in monocytes.ConclusionsDevelopment of lymphopenia from neoadjuvant chemotherapy was not associated with pCR in patients with TNBC. However, lower absolute circulating monocytes after neoadjuvant chemotherapy was associated with improved outcomes.

5030 Background: Neoadjuvant cisplatin-based combination chemotherapy (NAC) improves survival in muscle invasive bladder cancer (MIBC). However, response rates and survival remain suboptimal. We sought to evaluate the efficacy, safety and tolerability of cisplatin cabazitaxel combination in this patient group. Methods: A phase 2 single arm trial (Simon 2 stage), to recruit at least 26 evaluable patients was designed with 80% power to detect the primary endpoint, objective response rate (ORR) of &gt; 35%. ORR was defined as pathological complete response (pCR) plus partial response (pathological downstaging), measured by pathologic staging (T2 or greater at diagnosis, to T1 or less at radical cystectomy). Treatment was with Cisplatin 70mg/m2 and Cabazitaxel 15mg/m2 on day 1 of a 21 day cycle, for 4 cycles prior to surgery. Toxicity was recorded using CTCAE v.4.03. Quality of Life (QoL) data were collected at baseline, prior to each cycle of chemotherapy and at 3-5 weeks after 4th cycle of chemotherapy using EQ-5D and EORTC QLQ-C30, BLM30 questionnaires. Results: Objective response was seen in 15 out of 26 evaluable patients, 57.7% and over a third of patients achieved pCR (9/26; 34.6%). 78% (21/27) of patients completed all cycles of treatment, with only 6.7% of the reported adverse events (AEs) being graded 3 or 4. There were 6 treatment related SAEs reported but no SUSARs. In patients who achieved objective response the median progression free (PFS) and overall survival (OS) were not reached (median follow up: 41.5m). In contrast, median PFS (7.2m) and OS (16.9m) were significantly worse (p = 0.001) in patients who did not respond. Response rates for EORTC QLQ-C30, BLM 30 and EQ5D questionnaires was 70.4, 70.4 &amp; 63% respectively, at end of treatment. There was no significant difference in EORTC QLQ C30 summary, global health scores and EQ5D score with treatment. There was a significant decline in mean QLQ C30 domain scores after 1st cycle compared to baseline, but no further deterioration with subsequent cycles of chemotherapy. Conclusions: Cabazitaxel with cisplatin as NAC of MIBC can be considered a safe, well-tolerated and effective regimen with higher pCR rate of 34.6%. This compares favorably to that with Cisplatin/Gemcitabine (23-26%). Minimal changes in Global Health &amp; EQ5D observed during NAC further demonstrates the excellent tolerability of this regimen and to our knowledge are the first data regarding QoL in NAC in MIBC. These results warrant further evaluation in a larger phase 3 study. Clinical trial information: 2011 004090 82 .